Abstract

Background

RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly
frequent in the human transcriptome, largely due to the presence of inverted Alu repeats
and their ability to form double-stranded structures – a requisite for ADAR editing.
While several hundred thousand editing sites have been identified within these primate-specific
repeats, the function of Alu-editing has yet to be elucidated.

Results

We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective
editing in cis on sites located several hundred nucleotides from the Alu elements. Furthermore,
a computational analysis, based on available RNA-seq data, finds that site-selective
editing occurs significantly closer to edited Alu elements than expected. These targets
are poorly edited upon deletion of the editing inducers, as well as in homologous
transcripts from organisms lacking Alus. Sequences surrounding sites near edited Alus
in UTRs, have been subjected to a lesser extent of evolutionary selection than those
far from edited Alus, indicating that their editing generally depends on cis-acting Alus. Interestingly, we find an enrichment of primate-specific editing within
encoded sequence or the UTRs of zinc finger-containing transcription factors.

Conclusions

We propose a model whereby primate-specific editing is induced by adjacent Alu elements
that function as recruitment elements for the ADAR editing enzymes. The enrichment
of site-selective editing with potentially functional consequences on the expression
of transcription factors indicates that editing contributes more profoundly to the
transcriptomic regulation and repertoire in primates than previously thought.